What research is being done regarding osteoporosis?

Osteoporosis is thought of as a bone-weakening ailment that is mostly a problem for older women. But now doctors say it's striking younger patients. Informed Patient columnist Laura Landro reports on Lunch Break. Photo: Getty Images.

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Researchers take a major step towards better diagnosis and treatment of osteoporosis, says new research. A new target that may be critical for the treatment of osteoporosis, a disease which affects about 25% of post-menopausal women, has been discovered by a group of researchers in The Netherlands and in Germany. This week features the The European Human Genetics Conference 2014. (European Society of Human Genetics).

Professor Brunhilde Wirth, Head of the Institute of Human Genetics, University of Cologne, Germany, will tell the annual conference of the European Society of Human Genetics on June 1, 2014 (Sunday) that new studies in zebrafish and mice have shown that injection of human plastin 3 (PLS3) or related proteins in zebrafish where PLS3 action has been suppressed can replace its loss and repair the bone development anomalies associated with this deficiency. Furthermore, overexpression of human (PLS3) in normal mice had a significant impact on bone development and maintenance, making them more resistant to fractures.

The results came as a surprise to the researchers, since mutations in the PLS3 gene had not previously been known to be related to osteoporosis and fractures, or to play a role in bone formation

"In our most recent research, we started out by using zebrafish embryos in which PLS3 was knocked-out and studying their development at the three and five day-old stage," says Professor Wirth, according to the May 30, 2014 news release, Researchers take a major step towards better diagnosis and treatment of osteoporosis, "and we found that they had massive impairment of craniofacial skeletal development. However, this was fully restored when we added human PLS3. The same thing happened when we added two other proteins, actinin 1 and actinin 4, F-actin proteins2 which are involved in 'bundling' or building the 'scaffolding' for cells, and it seems that these proteins can compensate for the loss of PLS3. Thus we have been able to verify the essential role of actin in bone development and maintenance."

The subsequent mouse studies confirmed the findings in zebrafish, the researchers say, and open up possibilities for new treatments

They now intend to use PLS3 knock-out mice, where the PLS3 gene has been removed, in the search for the disease-causing mechanism involved. PLS3 is expressed in three different types of cells - osteocytes and osteoclasts, both involved in bone growth and remodeling, as well as in muscle cells. Using a transgenic mouse that overexpresses PLS3, they will also investigate whether this overexpression could be effective in other diseases involving in bone weakness.

"Since we know that about five percent of the human population expresses higher than normal levels of PLS3, we can hypothesise that these people may be protected against osteoporosis," says Professor Wirth, according to the news release. Once the researchers understand the exact disease-causing mechanism, it may be possible to translate the knowledge into therapy, they say.

What's protective against spinal muscular atrophy?

PLS3 overexpression is also protective against spinal muscular atrophy, the second most frequent autosomal recessive disorder in humans. This implies that understanding the protective role of PLS3 is crucial in both disorders.

"We are currently trying to unravel the whole protein network and, once we have understood the signalling pathways influencing PLS3 expression, we should be able to identify drugs or molecules that influence PLS3 expression or actin proteins," she says, according to the news release. Osteoporosis affects not only post-menopausal women, but also older men, and the condition currently causes more than 8.9 million fractures per year or an osteoporitic fracture every three seconds.

A fracture every three seconds

Worldwide one in three women over 50 will experience fractures due to osteoporosis, as will one in five men. Currently, emphasis for sufferers is on the prevention of falls that can cause broken bones. Although bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained an osteoporotic fracture, they are otherwise of little use.

"Osteoporosis poses an urgent health problem that is going to become more important as years go with the numbers of elderly people in the community continuing to increase," says Professor Wirth, according to the news release. "Although in itself it is not a fatal illness, large numbers of people die prematurely as a result of health complications following falls. We believe that our work has led to a better understanding of the condition and has pointed the way towards improved diagnosis and prevention, and, we hope, an effective treatment in the future."

F-actin is a multi-functional filamentous protein essential for regulating the mobility and contraction of cells. An autosomal recessive disorder is one where two copies of an abnormal gene must be present in order to the disease or condition to develop.

Why prescribe statins or blood thinners to people in the late stages of a terminal illness?

When people are in the late stages of a terminal illness and still on drugs that won't see benefits for years, drugs unrelated to their particular terminal illness, drugs that cost a lot of money, may have unwanted side effects, and usually unwanted if a change in diet can achieve similar results, do they finally feel they're free at last to use food as medicine for possible healing purposes, or do they conclude that they're not getting enough treatments?

The finding addresses a thorny question in treating people with life-limiting illnesses: When, if ever, is it appropriate to discontinue medications prescribed for other conditions that will likely not lead to their death?

In an analysis presented at the American Society of Clinical Oncology annual meeting in Chicago, the researchers reported that discontinuing statins in patients with advanced illnesses resulted in improved overall quality of life, lower costs and no increased deaths. In fact, the patients who stopped taking statins appeared to live slightly longer.

"When you look at the number of medications people take when they are dying, it doubles in the last year of life," said lead author Amy Abernethy, M.D., Ph.D., according to the May 30, 2014 news release, "Stopping statins may benefit terminally ill patients." Abernethy is the director of the Center for Learning Health Care at the Duke Clinical Research Institute and a member of the Duke Cancer Institute. Abernethy represented the Palliative Care Research Cooperative Group, a national research network focused on improving care for people with serious illnesses.

"Cancer patients, for example, take medications for pain, nausea and other problems associated with advanced disease," Abernethy said, according to the news release. "Many don't have an appetite, and simply swallowing medications can be a problem. So the issue is whether some longstanding medications such as cholesterol-lowering drugs might be safely discontinued, but there has been little research to help guide clinicians in making that recommendation."

Abernethy said the researchers identified statins as a good candidate to explore the issue, because the drug is widely prescribed and benefits can take years to accrue

Other drugs the researchers could eventually study include medications for blood pressure and blood clots. In their study of statins, Abernethy and colleagues enrolled 381 patients who faced the likelihood of dying within a year. All patients had been taking statins for at least three months; roughly half were randomized to continue taking the drug, the other half to discontinuing it.

The researchers followed the patients for up to a year to monitor survival, cardiovascular events and changes in quality of life. Among the 192 study patients who continued statins, the median survival was 190 days; the 192 participants who stopped taking the drugs had a median survival of 229 days.

Those who discontinued the drugs reported a better overall quality of life, particularly in their psychological wellbeing, and saved money: $716 per person over the course of the trial for name-brand drugs, and $629 for generics

Using U.S. population estimates, the researchers reported that as much as $603 million a year could be saved if patients in the late stages of fatal illnesses were to cut out statins. "This is a decision that needs to be discussed between patients and their doctors; it's not something that should be done independently or in a one-size-fits-all manner," Abernethy said, according to the news release. "But our study found that patients who discontinued statins reported improvements in quality of life. This runs counter to the idea that discontinuing a treatment would cause people to somehow feel as if they were getting less care or inadequate care."

Palliative care means extra support

Abernethy is a leading advocate for extending palliative care -- extra support from care teams to relieve both pain and improve quality of life -- to patients facing life-limiting illnesses. She said findings from this study should force new discussions.

"These are conversations that need to be had," she said, according to the news release. "This brings us to a new era of asking how to right-size care, and how to bring evidence to that issue. There is an important message here that taking things away isn't always bad."

For people predicted to live less than a year, why continue drugs for chronic illnesses that take years to progress, such as statins to lower cholesterol, blood thinners, or similar drugs not specifically related to treating the illness that's causing the person to be terminal? The answer may lie in making the drug manufacturers richer rather than suggesting a change in diet, fixing a nutrition issue if the food essence is not being absorbed, or suggesting activities to improve the quality of life for the person terminally ill?

It's noteworthy that patients who did stop their statins, according to the research, lived somewhat longer. It's also noteworthy that nothing is mentioned about any nutritional changes, such as denser nutrition, as many terminally ill patients have little or no appetite, often due to the type of medicines they take specifically for their terminal illness, as compared to chronic progressive health issues such as measuring cholesterol levels in a terminally-ill patient. How few doctors not practicing functional/integrative medicine are even aware of which dietary changes, plant extracts, and other such dietary approaches have what type of effects on patients or what nutrients have helped in various validated studies of food as medicine. You may wish to see the UC Health article "Food as medicine."

That article says the Center for Health and Nutrition Research (CHNR) at UC Davis received $6.4 million from the Vitamin Case Consumer Settlement fund, which was used to fund 33 research projects. Several are published in a special issue of California Agriculture, “Food as medicine: Can what we eat help cure what ails us?” To read the articles and issue in full, go to this site.

It's noteworthy how few doctors working with terminally ill patients focus on micronutrients rather than prescription drugs such as statins or blood thinners. There's a whole world of nutrition articles that doctors can share with patients. For example, CHNR pilot projects focused on how micronutrients, biofactors and phytochemicals can help reduce the risk of chronic diseases.

How many doctors talk to their patients about the omega-3 fatty acids in foods such as walnuts, flax seeds and salmon? Some do, but when it comes to the situation with terminally ill patients, the family and the patient may not be told which foods may protect against a range of diseases associated with inflammation, including asthma and the hypertension-related inflammation that can damage kidneys or what foods have anti-cancer properties. Read more.

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